Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, Rome, Italy.
Clinical Cell Transplant Program (CCTP), Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
Expert Opin Drug Saf. 2022 Sep;21(9):1161-1170. doi: 10.1080/14740338.2022.2130889. Epub 2022 Oct 6.
Diabetic kidney disease (DKD) represents a leading cause of morbidity and mortality in subjects with diabetes and develops in more than one third of diabetic patients. Steroidal mineralocorticoid receptor antagonists (MRAs - eplerenone and spironolactone) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF). However, in clinical practice the use of steroidal MRAs is limited by the significant risk of hyperkalemia, especially in patients with impaired renal function. Finerenone, a novel nonsteroidal MRA, shows a higher selectivity and binding affinity for mineralocorticoid receptor (MR) compared to steroidal MRAs and has been shown to reduce chronic kidney disease (CKD) progression and cardiovascular mortality in patients with CKD and T2DM.
This review summarizes the current evidence on efficacy and safety of finerenone in the treatment of patients with CKD and T2DM, and discusses its mechanisms of action investigated in preclinical studies.
Pharmacological properties of finerenone and its unique tissue distribution are responsible for a lower risk of hyperkalemia. Therefore, finerenone represents a valuable therapeutic tool in patients with CKD/diabetic kidney disease (DKD). Recent studies have shown that finerenone delays the progression of CKD and reduce cardiovascular events in patients with DKD, highlighting its safety and efficacy in this high-risk population.
糖尿病肾病(DKD)是糖尿病患者发病率和死亡率的主要原因之一,超过三分之一的糖尿病患者会发展为 DKD。甾体类盐皮质激素受体拮抗剂(MRA-依普利酮和螺内酯)可降低射血分数降低的心力衰竭(HFrEF)患者的死亡率。然而,在临床实践中,甾体类 MRA 的使用受到高血钾风险的限制,尤其是在肾功能受损的患者中。非甾体类 MRA 非奈利酮与甾体类 MRA 相比,对盐皮质激素受体(MR)具有更高的选择性和结合亲和力,已被证明可降低慢性肾脏病(CKD)和 2 型糖尿病(T2DM)患者的 CKD 进展和心血管死亡率。
本文综述了非奈利酮在治疗 CKD 和 T2DM 患者方面的疗效和安全性的现有证据,并讨论了其在临床前研究中调查的作用机制。
非奈利酮的药理学特性及其独特的组织分布使其发生高钾血症的风险较低。因此,非奈利酮代表了 CKD/糖尿病肾病(DKD)患者的一种有价值的治疗工具。最近的研究表明,非奈利酮可延缓 CKD 的进展,并降低 DKD 患者的心血管事件发生率,突出了其在这一高危人群中的安全性和疗效。